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Brief Communications: Clinical Transplantation


Johnson, Lynt B.1,2; Kuo, Paul C.1; Dafoe, Donald C.3; Drachenberg, Cinthia B.4; Schweitzer, Eugene J.1; Alfrey, Edward J.3; Ridge, Linda A.1; Salvatierra, Pamela3; Papadimitriou, John C.4; Mergner, Wolfgang J.4; Bartlett, Stephen T.1

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A major impediment to renal transplantation as the optimal treatment for end stage renal disease is the severe shortage of donor organs. Moreover, the traditional brain dead cadaver donor pool has shifted to include a greater percentage of older donors and donors with longstanding hypertension due to successful efforts of seatbelt and mandatory helmet laws, which have reduced traumatic fatal closed head injuries. Therefore, alternative approaches to traditional organ donor selection have been proposed. These unconventional approaches have included utilizing organs from non-heart-beating donors, as well as organs from donors that are considered marginal because of organ dysfunction, donor age, intercurrent chronic illness or adverse histology (1-3). The potential benefit of transplanting such kidneys (freeing the recipient from dialysis) is gained by accepting a certain risk (the kidney might function poorly, or not at all). The decision to utilize kidneys from donors that are considered marginal is mainly based on evaluation of a combination of factors that may affect the ultimate performance of the graft. The goal is to transplant a sufficient, viable nephron mass.

Donor past medical history, renal function, cold ischemic time, and gross anatomic abnormalities are factors often weighed when evaluating cadaver kidneys. In questionable cases, the histologic appearance of the kidney is often very helpful. Many centers employ routine biopsy and histologic examination of kidneys from donors above the age of 55, or those with a prolonged history of hypertension, diabetes, or other conditions that could compromise the function of the transplanted kidney (4). Such kidneys would generally be judged acceptable by the absence of significant abnormalities such as moderate or severe arteriolar hyalinosis or sclerosis, interstitial inflammation or fibrosis, and tubular atrophy or glomerulosclerosis, and the presence of satisfactory renal function in the donor. As the severity of the histopathologic features worsens or the glomerular filtration rate declines, the decision to utilize the kidney becomes more difficult. One must consider not only the baseline pathology, but also the further detrimental effects of subsequent insults such as cold ischemia, rejection episodes, and exposure to nephrotoxic agents. This is particularly true in light of recent reports indicating that kidneys with preexisting renal injury or sub-optimal nephron mass may be more likely to deteriorate as a result of both immunologic and nonimmunologic factors. Generally, such kidneys are discarded after it is decided that transplantation of the kidney would result in a poor outcome based on these considerations. Herein, we propose that older donor kidneys with diminished glomerular filtration rate (GFR)* or kidneys with significant glomerulosclerosis due to longstanding hypertension that are otherwise destined for discard, can provide satisfactory renal function if both donor kidneys are transplanted into a single recipient.

We report the use of bilateral transplantation of paired adult renal allografts considered unsuitable for transplantation as single kidneys. Ten paired adult renal allografts, each from the same cadaver donor, were transplanted from 7/94 to 7/95. The decision to perform bilateral transplants was based on poor estimated donor glomerular filtration rate in older donor kidneys, along with unfavorable histologic features found on frozen section examination of the kidneys (Table 1). Mean donor age was 62.7±3.4. The three oldest donors were 68, 70, and 78 years old. The cause of death in nine of the ten donors was cerebrovascular accident; one donor died from a gunshot wound to the head. Eight of ten donors had a significant past history of hypertension.

Wedge biopsies for frozen section analysis were performed on six of the ten paired donor kidneys (Table 2). The tissue was immediately frozen in optimal cutting media (Miles Laboratory, Eikert, IN), and routine 4-μ frozen sections were examined. The remainder of the specimen was fixed in formalin and embedded in paraffin. Then 5-μ sections were stained with hematoxylin and eosin, PAS, and Masson's trichrome stain. Frozen section biopsies were reviewed prior to transplantation by the recipient surgeon and staff pathologist in all cases. Frozen sections were evaluated for the presence and degree of glomerulosclerosis, interstitial fibrosis, chronic interstitial inflammation, tubular atrophy, and vascular hyalinosis or sclerosis. The frozen section findings in three of six donor biopsies obtained demonstrated glomerulosclerosis in 10-20% of the glomeruli, while in the remaining three donor biopsies glomerulosclerosis was present in >20% of the glomeruli along with the presence of interstitial fibrosis, and vascular hyalinosis or sclerosis (Fig. 1). In addition, two biopsies demonstrated moderate interstitial lymphocytic infiltrates. Permanent sections were subsequently reviewed retrospectively by the same pathologist and surgeon and each was correlated with the frozen section description.

All paired kidneys were separated at the time of procurement and sequentially transplanted. Six paired kidneys were placed intraperitoneally, while the remaining four pairs were placed in bilateral retroperitoneal iliac fossa locations. Vascular anastamoses were performed in standard end-to-side fashion to the external iliac vessels. Bilateral extravesical ureteroneocystostomies were performed with mucosa-to-mucosa anastomosis under a muscular tunnel.

Recipients have been followed for an average of 6.5 months (range two to fourteen months). Two recipients required temporary dialysis for delayed graft function; the remaining eight patients had immediate graft function (80%). Late graft loss due to irreversible rejection occurred in one patient with six months of satisfactory graft function following patient noncompliance with the standard immunosuppression regimen. The remaining nine recipients (90.0%) had satisfactory posttransplant renal function after bilateral renal transplantation. Mean serum Crs at 1, 3, and 6 months were 1.8, 1.8, and 1.5 mg/dl, respectively. The calculated creatinine clearances (CrCl) obtained from 24-h urine collections in three recipients with long-term function were 32.0, 34.2, and 58.0 ml/min (Table 2). Mean CrCl was 43.2±3.4. Currently nine of ten recipients of bilateral renal transplants are dialysis-in-dependent with satisfactory graft function, for an overall graft survival of 90.0% and actuarial 1-year graft survival of 83.3%.

Assessment of donor renal function, cold ischemic time, presence of histologic evidence of significant acute or chronic injury, and the anticipated use of cyclosporine in the recipients, led us to surmise that outcome following transplantation of these grafts as single kidneys would result in unsatisfactory renal function in the recipients. In fact, all these kidneys had been previously refused by other transplant centers. Prior studies have shown that maintenance doses of cylcosporine can reduce GFR in a time-and dose-dependent manner by 50-70% (5). Moreover, although dose-related renal dysfunction is reversible, cyclosporine may also cause some permanent changes, such as ateriolopathy and interstitial fibrosis (6). Despite the presence of significant risk factors for a poor outcome in the donors, and the use of cyclosporine as maintenance immunosuppression in the recipients, graft function was satisfactory in nine of our ten patients.

There are emerging isolated case reports of long-term success in utilizing donor kidneys with glomerulosclerosis-however, experience with transplantation of older donor kidneys with extensive glomerulosclerosis and chronic vascular and interstitial changes has yielded poor long-term results (7,8). Many transplant centers routinely refuse donor kidneys with any degree of chronic glomerular, vascular, or interstitial change on biopsy. The method of bilateral renal transplantation has been reported for the transplantation of en bloc pediatric kidneys (9), but this is the first report of the use of bilateral renal transplantation of impaired adult kidneys. Since this technique allows a salvage of undesirable donor kidneys that would otherwise be discarded, it has the potential to increase the kidney donor pool. Short-term results have demonstrated satisfactory renal function in 90.0% of our patients. We caution against the overenthusiastic application of this approach. We advise the careful application of this technique to situations in which patients have limited access to dialysis or are functioning poorly on dialysis, and thus need transplantation as a last resort.

Figure 1
Figure 1:
Donor renal allograft biopsy with Masson's trichrome stain of representative area showing three sclerotic glomeruli with associated interstitial fibrosis and tubular atrophy.


Abbreviations: C, creatinine; CrCl, creatinine clearance; GFR, glomerular filtration rate.


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